Patterns in Use and Transplant Outcomes Among Adult Recipients of Kidneys From Deceased Donors With COVID-19.

Importance: While the COVID-19 pandemic enters a new phase and the proportion of individuals with a previous COVID-19 diagnosis increases, the national patterns in kidney use and medium-term kidney transplant (KT) outcomes among patients receiving kidneys from active or resolved COVID-19-positive donors remain unknown. Objective: To evaluate the patterns in kidney use and KT outcomes among adult recipients of kidneys from deceased donors with active or resolved COVID-19. Design, Setting, and Participants: This retrospective cohort study was conducted using national US transplant registry data from 35 851 deceased donors (71 334 kidneys) and 45 912 adult patients who received KTs from March 1, 2020, to March 30, 2023. Exposure: The exposure was donor SARS-CoV-2 nucleic acid amplification test (NAT) results, with positive NAT results within 7 days before procurement defined as active COVID-19 and positive NAT results 1 week (>7 days) before procurement defined as resolved COVID-19. Main Outcomes and Measures: Primary outcomes were kidney nonuse, all-cause kidney graft failure, and all-cause patient death. Secondary outcomes were acute rejection (ie, rejection in the first 6 months after KT), transplant hospitalization length of stay (LOS), and delayed graft function (DGF). Multivariable logistic regression analyses were performed for kidney nonuse, rejection, and DGF; multivariable linear regression analyses were performed for LOS; and multivariable Cox regression analyses were performed for graft failure and all-cause death. All models were adjusted for inverse probability treatment weighting. Results: Among 35 851 deceased donors, the mean (SD) age was 42.5 (15.3) years; 22 319 (62.3%) were men and 23 992 (66.9%) were White. Among 45 912 recipients, the mean (SD) age was 54.3 (13.2) years; 27 952 (60.9%) were men and 15 349 (33.4%) were Black. The likelihood of nonuse of kidneys from active or resolved COVID-19-positive donors decreased over time. Overall, kidneys from active COVID-19-positive donors (adjusted odds ratio [AOR], 1.55; 95% CI, 1.38-1.76) and kidneys from resolved COVID-19-positive donors (AOR, 1.31; 95% CI, 1.16-1.48) had a higher likelihood of nonuse compared with kidneys from COVID-19-negative donors. From 2020 to 2022, kidneys from active COVID-19-positive donors (2020: AOR, 11.26 [95% CI, 2.29-55.38]; 2021: AOR, 2.09 [95% CI, 1.58-2.79]; 2022: AOR, 1.47 [95% CI, 1.28-1.70]) had a higher likelihood of nonuse compared with kidneys from donors without COVID-19. Kidneys from resolved COVID-19-positive donors had a higher likelihood of nonuse in 2020 (AOR, 3.87; 95% CI, 1.26-11.90) and 2021 (AOR, 1.94; 95% CI, 1.54-2.45) but not in 2022 (AOR, 1.09; 95% CI, 0.94-1.28). In 2023, kidneys from both active COVID-19-positive donors (AOR, 1.07; 95% CI, 0.75-1.63) and resolved COVID-19-positive donors (AOR, 1.18; 95% CI, 0.80-1.73) were not associated with higher odds of nonuse. No higher risk of graft failure or death was found in patients receiving kidneys from active COVID-19-positive donors (graft failure: adjusted hazard ratio [AHR], 1.03 [95% CI, 0.78-1.37]; patient death: AHR, 1.17 [95% CI, 0.84-1.66]) or resolved COVID-19-positive donors (graft failure: AHR, 1.10 [95% CI, 0.88-1.39]; patient death: AHR, 0.95 [95% CI, 0.70-1.28]). Donor COVID-19 positivity was not associated with longer LOS, higher risk of acute rejection, or higher risk of DGF. Conclusions and Relevance: In this cohort study, the likelihood of nonuse of kidneys from COVID-19-positive donors decreased over time, and donor COVID-19 positivity was not associated with worse KT outcomes within 2 years after transplant. These findings suggest that the use of kidneys from donors with active or resolved COVID-19 is safe in the medium term; further research is needed to assess longer-term transplant outcomes.

Impact of antimetabolite discontinuation following cytomegalovirus or BK polyoma virus infection in kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) and BK polyoma virus (BKV) infection following kidney transplantation have been associated with allograft dysfunction and allograft loss. Reduction in immunosuppression is a mainstay of management yet has been associated with increased risk of rejection. According to international consensus guidelines, one approach to management of these viral infections is to discontinue the antimetabolite. Little is known surrounding long-term outcomes in these patients, and it remains unclear if consideration should be given to resuming the antimetabolite as variable re-escalation strategies have been reported. The objective was to describe episodes of rejection and identify risk factors for rejection following antimetabolite withdrawal after CMV or BKV DNAemia in kidney transplant recipients. METHODS: This single-center, retrospective review evaluated adult kidney transplant recipients with a serum CMV or BKV DNA PCR ≥500 copies/ml who underwent antimetabolite discontinuation. The primary outcome assessed was the incidence of biopsy-proven acute rejection (BPAR). RESULTS: One hundred fifty-nine patients were included. Overall, 14 patients (8.8%) experienced BPAR at a median of 1.6 years after antimetabolite discontinuation. Compared to CMV, discontinuation after BKV DNAemia was associated with a higher incidence of BPAR. Characteristics observed more frequently in patients with BPAR included younger age, female sex, higher initial viral load, and development of de novo donor-specific antibody (DSA). CONCLUSION: These findings suggest that antimetabolite discontinuation after CMV or BKV DNAemia in kidney transplant recipients is a reasonable and safe approach. Further prospective studies investigating optimal immunosuppression management following CMV or BKV DNAemia in kidney transplant recipients are warranted.

Clinical Experience with Extended-Release Tacrolimus in Older Adult Kidney Transplant Recipients: A Retrospective Cohort Study.

BACKGROUND: Extended-release tacrolimus (LCP-Tac) prescribing information states that there is insufficient data in older adult patients from which to make recommendations on use in this population. This study sought to provide information on de novo use of LCP-Tac in the older adult kidney transplant population. METHODS: This single-center retrospective study had two distinct objectives; to determine if weight-based doses of LCP-Tac differ based on recipient age and to compare safety and efficacy between LCP-Tac and immediate-release tacrolimus (IR-Tac) in older adult transplant recipients. Data was obtained through electronic chart review up to 2 years after transplant with censoring for graft loss and death. RESULTS: Weight-based doses were compared between patients aged ≥ 65 years (n = 84), 36-64 years (n = 64), and ≤35 years (n = 44). LCP-Tac weight-based doses were lower at all time points in patients ≥ 65 years of age. Both age and race significantly impacted required dose on linear regression. The doses required to achieve therapeutic tacrolimus troughs were significantly lower in all age groups compared with the current FDA de novo dosing recommendation. In the older adult population, graft outcomes and infectious and metabolic complications were compared between recipients of LCP-Tac (n = 84) and IR-Tac (n = 42). Within this cohort, there were no differences between LCP-Tac and IR-Tac on graft function, rejection, graft loss, death, cytomegalovirus viremia, BK viremia, hypertension, diabetes, alopecia, or tremor up to 2 years after transplant. CONCLUSIONS: Older adult recipients required significantly lower LCP-Tac doses compared with younger recipients and with the FDA-labeled starting dose. There were no differences in graft outcomes or adverse effects in older adult patients who received LCP-Tac versus IR-Tac.

Choice of Acid Suppressant Therapy and Long-Term Graft Outcomes After Kidney Transplantation.

STUDY OBJECTIVE: The purpose of this study was to comprehensively evaluate the long-term adverse effects of proton pump inhibitors (PPIs) compared with histamine-2 receptor antagonists (H2RAs) in kidney transplant recipients. METHODS: This retrospective cohort compared 582 patients treated with PPI with 705 patients treated with H2RA and evaluated adverse effects throughout their course of acid suppressant therapy to a maximum of nine years posttransplant. The primary outcome of interest was renal function at 1 year posttransplant; secondary outcomes included renal function at 30 days, 3, 5, and 9 years posttransplant as well as rejection, electrolyte and laboratory abnormalities, osteoporosis, pneumonia, and Clostridium difficile infections. RESULTS: Renal function did not significantly differ at any timepoint posttransplant. Rejection rates and Clostridium difficile infections were similar between groups; osteoporosis and pneumonia rates were numerically higher in the PPI treated arm but did not reach statistical significance. Proton pump inhibitor (PPI) treated patients were more likely to experience hypomagnesemia requiring supplementation. High dose PPI treated patients had significantly higher rates of pneumonia and osteoporosis compared with H2RA treated patients. Patients were maintained on PPI therapy for an average of 5 years and H2RA therapy for 3 years posttransplant, the majority without a clear indication for therapy. CONCLUSIONS: There was no difference in renal function, rejection, or graft loss between PPI and H2RA treated patients. The majority of patients were maintained on PPI therapy for several years posttransplant without a clear indication; critical evaluation of ongoing need for acid suppressant therapy in the posttransplant course should be an area of future focus.

Evaluation of leflunomide for the treatment of BK viremia and biopsy proven BK nephropathy; a single center experience.

BACKGROUND: BK virus reactivation is a significant complication following renal transplantation that can result in graft failure. Reduction of immunosuppression and substitution of leflunomide for mycophenolate mofetil (MMF) has been used to treat this entity. OBJECTIVES: To evaluate the use of leflunomide in BK viremia (BKV) and biopsy proven BK nephropathy (BKN) in kidney and kidney-pancreas transplant recipients. PATIENTS AND METHODS: We retrospectively reviewed 28 kidney and kidney-pancreas transplant recipients who had received leflunomide for BKV from January 2006 to November 2012. Demographics, time to BKV diagnosis, biopsy findings, rejection episodes, and laboratory data were recorded. RESULTS: The average (mean ± SD) time to BKV from time of transplant was 316.1 ± 368.0 days (62-1708 days). At time of diagnosis, 64% of patients had their maintenance immunosuppression reduced. The indications for leflunomide administration were; BKV and biopsy proven acute rejection (BPAR) (50%), biopsy proven BKN (18%), or persistent BKV (25%). Therapeutic levels (50-100 mcg/mL) were achieved in only 54% of patients, and 60% of them had required a leflunomide dose of at least 60 mg/day. BK virus was cleared from the serum on average of 151 ± 145.2 days (17-476 days). At study commencement, 29% of patients had remained on leflunomide due to persistent BKV. CONCLUSIONS: In our study, most patients required at least a 60 mg daily dose of leflunomide to achieve therapeutic levels and to clear the virus compared to the standard 40 mg daily dose. Delaying therapy may result in progressive BKV and BKN.